The objective of our research program is to characterize the hydrogen isotope exchange kinetics of single, assigned, amide protons in bovine pancreatic trypsin inhibitor (BPTI), and to interpret the kinetics in terms of the internal motions of the folded macrostate of globular proteins. Single proton hydrogen-deuterium exchange kinetics are followed by nuclear magnetic resonance spectroscopy. Research goals for the '80-'81 year are: a) to examine the effect of urea on the exchange of the slowest exchanging BPTI amide protons, b) to characterize the thermal unfolding transition of BPTI in 0.3 M KCl and 8 M urea by circular dichroism, c) to characterize the pH and temperature dependence of the exchange kinetics of the more rapidly exchanging protons in BPTI, d) to begin studies of exchangable amide protons in the interface of the BPTI-trypsin complex. The interface protons can be labelled with 1H while the interior protons in BPTI and trypsin are deuterated and therefore not observed. The differential labeling technique we will use for this is explained in our original proposal for this grant.